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Absolute hydration entropies of alkali metal ions from molecular dynamics simulations
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2009 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 30, 10255-10260 p.Article in journal (Refereed) Published
Abstract [en]

Molecular dynamics simulations in combination with the free energy   perturbation technique are used in this work to calculate absolute ion   hydration entropies. The hydration entropies for five alkali metal ions   are estimated from van't Hoff plots using hydration free energies   calculated at eight different temperatures. Considering that the   ion-water potentials were parametrized only on absolute hydration free   energies and ionic radii, the absolute hydration entropies agree very   well with experimental data. Simulation lengths of about 3 ns at each   temperature were required to achieve an uncertainty below 1 kcal/mol   for the entropic contribution to the hydration free energy (-T Delta   S-hyd). The uncertainties for the calculated entropies are typically   four times larger than for the free energies. The possibility to use   approximate approaches to calculate hydration entropies is also   investigated. The entropy of creating the uncharged van der Waals spheres in water correlates well with the solvent accessible surface area of the ions. The Born continuum model and the linear response   approximation cannot be used to predict the entropy of charging the van   der Waals spheres in water without introducing temperature dependent empirical parameters.

Place, publisher, year, edition, pages
2009. Vol. 113, no 30, 10255-10260 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-97217DOI: 10.1021/jp900818zISI: 000268231000030OAI: oai:DiVA.org:uu-97217DiVA: diva2:172051
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2010-07-19Bibliographically approved
In thesis
1. Challenges in Computational Biochemistry: Solvation and Ligand Binding
Open this publication in new window or tab >>Challenges in Computational Biochemistry: Solvation and Ligand Binding
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Accurate calculations of free energies for molecular association and solvation are important for the understanding of biochemical processes, and are useful in many pharmaceutical applications. In this thesis, molecular dynamics (MD) simulations are used to calculate thermodynamic properties for solvation and ligand binding.

The thermodynamic integration technique is used to calculate pKa values for three aspartic acid residues in two different proteins. MD simulations are carried out in explicit and Generalized-Born continuum solvent. The calculated pKa values are in qualitative agreement with experiment in both cases. A combination of MD simulations and a continuum electrostatics method is applied to examine pKa shifts in wild-type and mutant epoxide hydrolase. The calculated pKa values support a model that can explain some of the pH dependent properties of this enzyme.

Development of the linear interaction energy (LIE) method for calculating solvation and binding free energies is presented. A new model for estimating the electrostatic term in the LIE method is derived and is shown to reproduce experimental free energies of hydration. An LIE method based on a continuum solvent representation is also developed and it is shown to reproduce binding free energies for inhibitors of a malaria enzyme. The possibility of using a combination of docking, MD and the LIE method to predict binding affinities for large datasets of ligands is also investigated. Good agreement with experiment is found for a set of non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Approaches for decomposing solvation and binding free energies into enthalpic and entropic components are also examined. Methods for calculating the translational and rotational binding entropies for a ligand are presented. The possibility to calculate ion hydration free energies and entropies for alkali metal ions by using rigorous free energy techniques is also investigated and the results agree well with experimental data.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 62 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 432
Molecular biology, computer simulations, molecular dynamics, solvation free energy, Generalized-Born, Poisson-Boltzmann, ligand binding, binding free energy, linear interaction energy, binding entropy, hydration entropy, Molekylärbiologi
urn:nbn:se:uu:diva-8738 (URN)978-91-554-7200-9 (ISBN)
Public defence
2008-05-23, B7:101, BMC, Husargatan 3, Uppsala, 13:15
Available from: 2008-04-29 Created: 2008-04-29Bibliographically approved

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